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Updated: May 14, 2026
Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
Published on: May 2, 2022
Expression of stem cell factor in gastrointestinal stromal tumors: Implications for proliferation and imatinib
Xiao-Wei Hou1, Chen-Guang Bai, Xiao-Hong Liu
1Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433; ; Department of Oncology, 401 Hospital of PLA, Qingdao, Shandong 266071;
Abstract:
KIT autophosphorylation caused by mutation of KIT is considered to be a critical mechanism for the oncogenesis of gastrointestinal stromal tumors (GISTs). However, little is known regarding whether stem cell factor (SCF), the KIT ligand, is able to induce the proliferation of GIST cells by activating the wild-type KIT receptor in GISTs. Imatinib, a tyrosine kinase inhibitor, has been demonstrated to be effective as treatment for the majority of GISTs. However, primary resistance to imatinib in GISTs with wild-type KIT and acquired resistance in GISTs with mutant KIT are becoming increasingly significant problems. The aims of this study were to detect the expression and function of SCF in 68 GIST samples, and to explore the relationship between SCF activity and imatinib resistance using immunohistochemical staining and western blot analysis. Results showed abundant expression of SCF in GISTs and demonstrated that SCF is capable of enhancing GIST cell proliferation. Similar to its ineffectiveness in wild-type GISTs, imatinib also failed to inhibit SCF-induced KIT activation in GISTs with mutant KIT. We also found increased SCF expression in GIST cells treated with imatinib. Overall, our results indicated that SCF-induced KIT activation is a novel essential pathway for the proliferation of GISTs. Imatinib was not able to inhibit the activity of SCF, while it promoted the expression of SCF, which may have contributed to acquired imatinib resistance.
Insights
Stem cell factor (SCF) drives gastrointestinal stromal tumor (GIST) cell proliferation by activating KIT. Imatinib resistance may stem from SCF’s promotion of KIT activation and increased SCF expression in GISTs.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Gastrointestinal stromal tumors (GISTs) are driven by KIT mutations causing autophosphorylation.
- Imatinib is effective for most GISTs, but resistance remains a significant challenge.
- The role of stem cell factor (SCF) in activating wild-type KIT and GIST proliferation is not well understood.
Purpose of the Study:
- To investigate the expression and function of SCF in GIST samples.
- To explore the link between SCF activity and imatinib resistance in GISTs.
Main Methods:
- Immunohistochemical staining of 68 GIST samples.
- Western blot analysis to assess protein expression and activation.
- Evaluation of SCF expression and its effect on GIST cell proliferation.
Main Results:
- Abundant SCF expression was detected in GIST samples.
- SCF significantly enhanced GIST cell proliferation.
- Imatinib did not inhibit SCF-induced KIT activation in GISTs, irrespective of KIT mutation status.
- Increased SCF expression was observed in GIST cells treated with imatinib.
Conclusions:
- SCF-induced KIT activation represents a novel pathway crucial for GIST proliferation.
- Imatinib's inability to inhibit SCF activity and its promotion of SCF expression may contribute to acquired imatinib resistance in GISTs.
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